Denosumab Therapy in the Management of Aneurysmal Bone Cysts: A Comprehensive Literature Review

Abstract

Aneurysmal bone cysts (ABCs) are uncommon lesions that involve the axial and appendicular bones. Although biologically benign, ABCs have the tendency to assume an aggressive behavior causing local destruction of the underlying bone and neighboring soft tissues. Morphologically, ABCs are composed of cyst-like cavities filled with blood and bounded by an array of diverse cells including fibroblasts, inflammatory infiltrates and osteoclast-like multinucleated giant cells. From a molecular perspective, the osteoclast-like multinucleated giant cells harbor high expression of receptor activator of nuclear factor kappa B (RANK) receptors, whereas the neoplastic stromal cells harbor high expression of RANK ligand (RANKL). The RANK-RANKL interaction has been implicated in the carcinogenesis of ABCs and giant cell tumor of bones (GCTBs). Currently, the optimal management of ABCs remains a hotly debated topic. There are a multitude of treatment modalities (that is, surgery, sclerotherapy, radiotherapy and selective arterial embolization), and each modality has its own benefits, morbidity and risk of complications. The local aggressiveness of ABC and its high rates of relapse following treatment has demanded the march towards discovering more innovative therapies. One of such therapies is denosumab, a monoclonal antibody targeted against the RANKL. Denosumab is already approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is unamenable to surgery, or initial surgery is anticipated to result in significant morbidity. However, denosumab is not approved by the FDA for the management of ABCs. However, taking into consideration the morphological similarity between GCTBs and ABCs, some treating physicians have logically opted to use denosumab in an off-label manner to treat select ABCs. To the best of knowledge, no study has attempted to summarize the related literature on the use of denosumab in ABCs. Therefore, the primary aim of this study is to narratively review all the available literature about the efficacy and safety of the use of off-label denosumab in the management of patients with ABCs.

USP6-Associated Neoplasms: A Rapidly Expanding Family of Lesions

“…82 Notwithstanding the fact that surgery is the cornerstone of curative treatment, it has been shown that denosumab is an effective therapeutic option for ABC when resection is contra-indicated because of mutilating surgery. [83][84][85] Discussion USP6-rearrranged neoplasms share many similarities. Clinically, they usually occur in young adults and they are located in superficial or deep soft tissue and bone.…”

Role of cancer stem cells in the development of giant cell tumor of bone

“…This fact was confirmed with the help of immune-histochemical study in which osteoclast specific monoclonal antibodies were used [60]. GCTBs undergo secondary modifications including aneurysmal bone cyst (ABC) modification, foamy histiocytic combinations and responsive bone or osteoid production [61]. It has been found that several types of bone lacerations involving osteoclastic giant cells such as; osteosarcoma, primary ABC, non-ossifying fibroma, chondroblastoma, brown tumor (hyperparathyroidism), giant cell reparative granuloma and the giant cell-rich type specifically exhibit much more distinction than GCTB.…”

Aneurysmal bone cyst in thoracolumbar spine

“… 12 Denosumab has traditionally been used to treat giant cell tumor of bones, with which ABCs share some pathological features, and are now being used to manage ABCs in an off-label manner. 1 In particular, the use of denosumab for spine or pelvic ABCs is especially important as surgical outcomes in those areas may lead to serious morbidity. 12 While not yet approved by the Food and Drug Administration, several case series have been published and the existing literature suggests that Denosumab therapy is an effective therapy for ABC.…”

“…The literature supports that Denosumab leads to favorable clinical and radiological response, which has also been demonstrated in the case of the patient in this case report. 1 …”

“…Denosumab is a human monoclonal antibody that binds to the human RANK ligand (RANKL) on the surface of osteoclasts and their precursors, inhibiting osteoclast formation, function and survival, leading to decreased bone loss and destruction. 1 Plan for re-evaluation in a few months to assess the need for surgery to stabilize the spine. The patient was started on Denosumab monthly subcutaneous injections.…”